The purpose of this study is to elucidate key steps in the processes leading to dental caries and the prevention of their formation. Although there has been a dramatic decrease in incidence, dental caries continue to be one of the most prevalent diseases throughout the world. The apparent inability to eradicate dental caries stems, in part, from the fact that several critically important aspects remain unclear, although major features of this disease have been established. Of particular importance are the factors which influence the degree of saturation with respect to enamel mineral of the extracellular aqueous phase of dental plaque, plaque fluid. Most important among these factors are the release of mineral ions present in dental plaque and the presence of inherent buffering species in plaque fluid. These factors counteract the effects of organic acids produced by plaque bacteria through the fermentation of dietary carbohydrate. Importantly, the frequency of acid production results in bacterial shifts towards a more cariogenic microflora. The proposed studies will provide direct evidence for the nature of mineral ion (Ca, PO4 and F) reservoirs in dental plaque and the mechanism for enhancing their accumulation and subsequent release, as a means to reducing the cariogenic potential of plaque. Key buffering components in dental plaque fluid will be identified and related to health. Furthermore, the proportions of predominant putative cariogenic microorganisms in plaque will be determined using cultural procedures and specific oligonucleotide probes. The cariogenic potential of plaque will be assessed through the chemical analysis of plaque fluid (concentrations of individual organic acids, inorganic ions, phosphate, carbonate, pH, fluoride and calcium activity). Plaque fluid will be obtained from plaque associated with sound and white-spot enamel from individuals with well-defined caries histories, before and after sucrose exposure. Using these data, degree of saturation with respect to enamel mineral will be calculated. The influence of natural and artificially enhanced mineral ion reservoirs in dental plaque will be studied, with emphasis on the availability of these ions (particularly fluoride) following acid production. The relevance of these in vivo findings will be assessed through in vitro experiments on enamel demineralization and acid production (by plaque bacteria) using solutions mimicking plaque fluid compositions. The long-term goal is to provide a unified picture of the caries process to be used in the design of improved delivery mechanisms for mineral ions, the assessment of caries risk, and the development of relevant in vitro models.